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ENGINEERING THE COMPLEX ELECTRICAL RESPONSE OF METALLIC CLUSTER-ASSEMBLED FILMS FOR NEUROMORPHIC COMPUTING APPLICATIONS
No full textMammalian brain outperforms modern computers in executing complex tasks with high energy efficiency. These capabilities rely on the processing of stimuli by a network consisting in thousand billion neurons intricately interconnected through synapses. Neurons integrate signals in a non-linear way. Synapses can modulate their effectiveness according to stimuli (synaptic plasticity), providing the basis for learning. Nontrivial responses to stimuli are due to the collective dynamics regulating the network operations along with network topology.
Neuromorphic Computing (NC) draws inspiration from the structure and operation of the brain to offer an alternative to the present Von Neumann paradigm of computation. Metallic cluster-assembled films (MCAFs) constitute a potential physical substrate for this scope due to their topological complexity, non-linear conduction properties, and plasticity.
A key role in determining MCAF conduction properties is played by their ability to undergo reversible structural modifications, thus producing changes in their electric conductivity. This phenomenon is referred as Resistive Switching (RS). Even if MCAF based devices have been already exploited in different computing tasks, we still have poor insight on the physics underlying the complex dynamics that govern RS activity. The main goal of my thesis is to exploit a novel approach relying on micro-thermography to characterize the evolution of conductivity in MCAF and gain a deeper understanding of this rich phenomenology. My analysis led to the identification of “switching sites” undergoing the structural modifications responsible of RS. This strategy also allowed to study the statistical properties of RS in space and time, unveiling the presence of non-trivial correlations in these systems. My analysis also highlighted the impact of sample geometry and dimension on the number and distribution of the switching regions. Furthermore, I probed the electrical response to different stimuli, and I observed stereotyped behaviours that emerge from the average response of the switching regions. Modelling the deterministic component of the electrical response, offers the possibility to enhance controllability of MCAF based devices, while the intrinsic stochasticity provides a natural mechanism for efficient state-space exploration, ultimately supporting efficient programmability of such systems
HIGH-THROUGHPUT PROFILING OF INNATE IMMUNE CELLS TO UNVEIL TUMOR ESCAPE MECHANISMS IN MATCHED COLORECTAL CANCER AND LIVER METASTASES
No full textColorectal cancer (CRC) represents one of the leading global health burdens, with the liver being its predominant site of distant metastasis. A significant proportion of patients with colorectal liver metastases (CRLM) are diagnosed with synchronous lesions (sCRLM), identified at or shortly after diagnosis of the primary tumor, a clinical scenario linked to aggressive disease and poor outcomes. A major clinical challenge in this setting is that the majority of CRCs with liver metastasis are microsatellite stable or low instable (MSS or MSI-L, respectively), tumor types largely unresponsive to immune checkpoint (IC) therapies. Indeed, MSS/MSI-L tumors display "immune cold" microenvironments dominated by immunosuppressive mechanisms, which severely constrain treatment options. This unmet clinical need highlights the importance of dissecting the immune microenvironment of sCRLM, to identify early drivers of metastatic progression and highlight immunological features with therapeutic potential, ultimately supporting a new immune-weighted stratification of patients for novel therapeutic approaches.
To this end, we combined single-cell transcriptomic with paired V(D)J profiling to generate a multi-compartmental innate immune map of synchronous CRC and matched sCRLM, together with circulating blood samples.
Our analyses revealed that Tumor-Associated Macrophages (TAMs) and Dendritic Cells (DCs) emerged as dominant players of the tumor microenvironment (TME) along divergent tumor-specific trajectories. In CRC, TAMs were enriched in inflammatory states that paradoxically supported immune activation while simultaneously laying the groundwork for metastatic dissemination. Conversely, CRLM was dominated by proliferative CTLA4high immunoregulatory TAMs, whose higher frequencies were associated with shorter disease-free survival and worse prognosis. Furthermore, we identified two CRLM-specific TAM subsets characterized by IL7R expression and a cytotoxic/NK-like signature, suggesting unconventional differentiation trajectories or functional mimicry through trogocytosis. In parallel, DCs displayed a CRLM-specific developmental program in which cDC1 subsets differentiated into immunoregulatory LAMP3+ DCs (mregDCs) enriched for IDO1 expression and immune checkpoint ligands.
Natural Killer (NK) and Innate Lymphoid Cells (ILCs) showed strikingly distinct patterns between blood and tumor tissues. Circulating NK cells followed a canonical CD56bright-to-CD56dim trajectory, which bifurcated into a conventional cytotoxic-high branch and into a disease-specific cytokine hepatic-primed one. In sharp contrast, within CRLM the CD56bright population expanded dramatically compared to circulation, and diversified into IFNG-activated, cytotoxic-enriched, and stress-adapted states, with no developmental connection to hepatic CD56dim NK cells. Importantly, CRLM-associated CD56bright NK cells displayed concurrent upregulation of effector programs and multiple inhibitory receptors, including TIGIT, CXCR4, and SIGIRR, reflecting a paradoxical state of activation restrained by layered inhibitory checkpoints.
Finally, integrative analyses resolved a highly heterogeneous γδ T cell landscape across blood, CRC, and CRLM. Vδ1 T cells predominated in all compartments, with an inversion of the expected Vδ2 dominance in circulation, indicating disease-associated remodeling. Gene co-expression analysis revealed tissue-specific functional signatures, including IFNG-driven activation programs in tumors, cytotoxic/TEMRA modules in blood, and residency/regulatory features in CRC. By integrating TCR clonotype tracking, we uncovered direct evidence of active trafficking of identical γδ T clonotypes from blood to CRLM. Crucially, these clonotypes underwent compartment-specific functional rewiring, with cytotoxic programs preserved in circulation, whereas intrahepatic counterparts with the acquisition of exhaustion and stress signatures, highlighting the liver metastatic niche as a site of immune restraint.
Altogether, these findings delineate possible mechanisms involved in the early immunological remodeling that occurs in synchronous CRLM, showing how the hepatic niche actively reprograms myeloid, NK, and γδ T cell compartments toward states of restrained activation and immune escape. By linking clonal fate mapping with transcriptional states, this work provides a mechanistic framework for characterizing early immune influences in synchronous CRLM, reframing the liver not as a passive metastatic destination but as an active architect of immune escape. Such mechanistic insights not only expand the understanding of metastatic immune biology but also point toward new opportunities for therapeutic innovation, by paving the way for novel immunotherapeutic strategies specifically targeting IC-resistant CRLM
L¿ 'AMNISTIA' IN ETÀ CLASSICA ED ELLENISTICA. STRATEGIE DI RICONCILIAZIONE E RIDEFINIZIONE DELLA CITTADINANZA A SEGUITO DI CONFLITTI INTERNI
No full textL’indagine si configura come un’analisi diacronica dell’evoluzione del lessico dell’amnistia greca, a partire dall’espressione μὴ μνησικακεῖν fino al termine ἀμνηστία. Il primo capitolo esamina l’uso del verbo μνησικακέω nel V secolo, evidenziando una connotazione negativa che ne favorì l’uso, con negazione anteposta, per designare una rinuncia alla vendetta, come nel celebre caso dell’amnistia ateniese del 403 a.C. Sebbene la storia degli studi abbia consolidato l’idea di μὴ μνησικακεῖν come formula tecnica, l’analisi mostra come tale uso sia stato costruito ad hoc nel contesto postbellico di Atene. L’inquadramento teorico fa ricorso al modello della 'path dependence', spiegando la necessità di riforme istituzionali (tra cui la παραγραφή e la limitazione temporale della retroattività legislativa) come strategie di 'conversion', atte a reinterpretare norme esistenti. Il secondo capitolo problematizza ulteriormente il concetto di amnistia, distinguendolo da altri atti di clemenza e di rimpatrio degli esuli. Alcuni casi apparentemente pertinenti, come il decreto di Patroclide (405 a.C.), non sono ritenuti affidabili. Inoltre, il μὴ μνησικακεῖν si rivela essere rivolto a tutelare soprattutto chi era rimasto in città, piuttosto che gli esuli rientranti. I capitoli terzo e quarto approfondiscono l’uso del sintagma nelle fonti epigrafiche, mettendo in discussione il suo presunto valore tecnico-giudiziario, e lo rapportano a espressioni alternative di divieto di perseguire in giudizio – spesso di natura preventiva, come nel caso dei trattati di simpolitia. Infine, il quinto capitolo analizza i termini ἄδεια e ἀμνηστία, confermando che quest’ultima rappresenta, in epoca ellenistica, l’equivalente semantico di μὴ μνησικακεῖν. Il lavoro comprende un catalogo di 29 attestazioni coerenti con la definizione di amnistia adottata, coprendo un arco temporale dal 490 all’inizio del II secolo a.C.This study constitutes a diachronic analysis of the evolution of the vocabulary of Greek amnesty, tracing the development from the expression mē mnēsikakein to the term amnēstia. The first chapter investigates the use of the verb mnēsikakeō in fifth-century literary and epigraphic sources, highlighting its inherently negative connotation. This negative value favoured the use of the negated form mē mnēsikakein – rather than mē timōrein – to effectively express a renunciation of vengeance. Although the phrase has come to be regarded as a technical term for amnesty, the study argues that its juridical meaning was deliberately constructed in the context of the Athenian civil reconciliation. Prior to 403 BCE, mnēsikakeō had no procedural connotation; its transformation reflects a strategic reinterpretation of language to suit political aims. This process challenges the principle of institutional conservatism – commonly explained by the path dependence model – according to which institutional change entails high costs and requires transitional reforms. Such reforms in Athens included the introduction of paragraphē (Isoc. 18.2) and the law restricting the retroactive applicability of legislation (Andoc. 1.89), understood as instruments of institutional conversion.
The second chapter reassesses the definition of “amnesty,” distinguishing it from acts of clemency or repatriation of exiles. Some seemingly relevant cases, like the Patroclides’ decree (405 BCE), are deemed unreliable. Instead, mē mnēsikakein typically protected those who remained in the city, not returning exiles. Chapters three and four explore epigraphic attestations, arguing against a purely legal reading of the formula, and compare it to alternative expressions of legal non-retaliation, often used to prevent civil wars, such as in sympoliteia treaties. The fifth chapter examines the terms adeia and amnēstia, concluding that the latter becomes semantically equivalent to mē mnēsikakein in the Hellenistic period. The study includes a catalogue of 29 cases of amnesty consistent with the adopted definition, spanning from 490 to the early second century BCE
NOVEL MOLECULAR CANDIDATES WITH PROPHYLACTIC AND THERAPEUTIC POTENTIAL AGAINST HIV AND MEASLES INFECTIONS
No full textLe vaccinazioni preparano il corpo a difendersi dai virus, riducendo notevolmente il rischio di infezione e, in particolare, di malattia grave e morte. La tesi in questione affronta due obiettivi principali basati su questa concezione: (1) esaminare vari frammenti derivati da un anticorpo anti-idiotipo come potenziali immunogeni per il virus dell'immunodeficienza umana di tipo 1 (HIV-1) e (2) sviluppare anticorpi terapeutici contro le complicanze del virus del morbillo (MeV) a livello del sistema nervoso centrale (SNC), il tutto in un contesto preclinico. Alla fine del 2024, più di 40 milioni di persone in tutto il mondo erano HIV-1 positive, con oltre 1.4 milioni di bambini di età compresa tra 0 e 14 anni. Sebbene la terapia antiretrovirale (ART) a lungo termine permetta di ridurre il carico virale a valori non rilevabili, attualmente non esiste un trattamento che eradichi completamente l'HIV-1. Pertanto, la necessità di un vaccino efficace sottolinea l'importanza della continua ricerca medica su nuove molecole, in particolare applicate alla vaccinoprofilassi. Nel corso degli anni, una serie di evidenze hanno suggerito che le immunoglobuline sviluppate contro la
regione idiotipica di un anticorpo anti-HIV-1 potrebbero avere un paratopo strutturalmente simile a quello dell'anticorpo primario. Questa somiglianza potrebbe permettere loro di legarsi all’antigene originale. Inoltre, grazie alle loro ridotte dimensioni, i frammenti di anticorpo ingegnerizzati offrono nuove opportunità biofarmaceutiche. Per questo motivo, il frammento
legante l’antigene (Fab), il frammento variabile a catena singola (scFv) e il minibody (Mb) ottenuti da un anticorpo anti-idiotipo HIV-1 (P1) sono stati somministrati in vivo sia in conigli che in primati non umani (NHP) applicando due protocolli di vaccinazione distinti. L'obiettivo era determinare se diversi frammenti derivati da un anticorpo anti-idiotipo potessero indurre una risposta immunitaria specifica contro la glicoproteina esterna gp120, il principale bersaglio anticorpale dell'HIV-1. Il formato Mb
VHVL si è rivelato l’unico altamente efficace nel generare elevati livelli di anticorpi anti-gp120 nei conigli. Questa scoperta è promettente e apre la possibilità per ulteriori studi su questo frammento ingegnerizzato progettato per funzionare come immunogeno per l’HIV-1. Al contrario, nessuno dei frammenti testati derivati da P1 ha mostrato di indurre una risposta umorale anti-gp120 HIV-1 negli NHP. Per valutare un potenziamento dell’immunogenicità e della qualità complessiva degli anticorpi elicitati, dovrebbero essere esplorate modifiche nei protocolli di immunizzazione vaccinale impiegati. I cambiamenti potrebbero includere la combinazione di più frammenti dell'anticorpo P1 con dosi di richiamo a base di costrutti
trimerici SOSIP e il cambio o l’impiego di combinazioni di adiuvanti. La seconda parte di questa tesi si concentra sul MeV, un'altra grave minaccia per la salute globale. Ad agosto 2025, negli Stati Uniti d’America sono stati ufficialmente riportati 32 focolai di morbillo, con il 92% dei casi tra individui non vaccinati. L'aumento dell’esitazione vaccinale contribuisce a una diminuzione della vaccinazione contro il MeV, arrivando globalmente, nel
2023, a 10.3 milioni di persone infette. Il MeV è altamente contagioso e, poiché non è stata raggiunta l'immunità di gregge, rappresenta una grave minaccia per tutte le popolazioni vulnerabili che non possono ricevere l’attuale vaccino vivo attenuato. Inoltre, quando l'infezione da MeV avviene in bambini di età inferiori ai 12 mesi, si verificano complicanze al sistema nervoso centrale (SNC), tra cui la letale panencefalite subacuta sclerosante (SSPE), che colpisce gli stessi bambini anni dopo l’eliminazione della
malattia, con un’incidenza di 1:609. In questa tesi, un 'cocktail di anticorpi' composto da tre anticorpi umanizzati anti-MeV (77.1, Y10F e H55) è stato inizialmente testato in vitro per valutare il suo potenziale sia profilattico che terapeutico. In sintesi, 77.1 si lega alla conformazione di pre-fusione della proteina F del MeV, stabilizzandola in uno stato intermedio. Y10F riconosce la regione apicale della proteina F, bloccandola nella conformazione di pre-
fusione, mentre H55 si lega alla proteina H, impedendo la sua interazione con il recettore e l'attivazione della proteina F. Pertanto, la combinazione di tutti e tre gli anticorpi ha comportato un significativo aumento della capacità inibitoria, indicando un'attività sinergica tra gli stessi. Successivamente, poiché le complicanze al SNC da MeV sono attualmente incurabili, una modifica di tre amminoacidi (M252Y/S254T/T256E [YTE]) nella frazione
costante (Fc) di 77.1 (77.1YTE) è stata testata in vivo per determinare se la stessa aumentasse la localizzazione dell'anticorpo nel SNC rispetto alla versione non modificata (77.1). Di conseguenza, 77.1YTE si localizza
efficientemente nel cervello, rimanendo rilevabile anche 168 ore dopo l'iniezione. Inoltre, 77.1YTE mantiene la capacità di legarsi alla conformazione naturale della proteina F del MeV, indicando che potrebbe essere efficace contro ceppi di morbillo che si diffondono nel SNC. Questo costituisce un primo, significativo progresso verso un potenziale utilizzo come approccio terapeutico.Immunizations prime the body to defend itself against viruses, significantly reducing the risk of infection and, more importantly, the risk of severe disease and death. This is the underlying idea of this thesis, and it addresses two major objectives: (1) to evaluate novel anti-idiotype antibody-derived fragments as potential Human Immunodeficiency Virus type 1 (HIV-1) immunogens, and
(2) to develop therapeutic antibodies against measles virus (MeV) central nervous system (CNS) complications; all in pre-clinical settings. As of 2024, more than 40 million people worldwide were living with HIV-1, including over 1.4 million children aged 0 to 14. Even though long-lasting antiretroviral therapy (ART) allows the decrease of the viral load to an undetectable value, there is currently no available treatment that completely eradicates HIV-1.
Therefore, the necessity of an effective vaccine emphasizes the medical need to continue researching novel molecules, and a prophylactic approach appears
promising. Over the years, different pieces of evidence have suggested that immunoglobulins generated against the idiotype region of an anti-HIV-1 antibody could have a paratope structurally similar to the primary antibody. This similarity could allow them to bind to the original target. Moreover, engineered antibody fragments also offer new biopharmaceutical opportunities because of their smaller size. For this reason, antigen-binding fragment (Fab), single-chain variable fragment (scFv), and minibody (Mb) derived from an anti-idiotype HIV-1 antibody (P1) were administered in vivo in both rabbits and non-human primates (NHPs) following two distinct vaccination protocols. The objective was to determine whether several anti-idiotype antibody-derived fragments could elicit a specific immune response against the outer envelope glycoprotein gp120, which is HIV-1’s main antibody target. Only the Mb VHVL format appeared to be highly effective in generating strong and long-lasting anti-gp120 antibodies in rabbits. This discovery is promising and raises the possibility of investigating this antibody-derived
fragment as an HIV-1 immunogen in further detail. Rather, NHPs did not exhibit a distinct HIV-1 anti-gp120 humoral response with none of the P1-derived fragments tested. Modifications in vaccine immunization, including combining multiple P1 antibody fragments while boosting with the trimeric SOSIP constructs, and either changing or employing adjuvant combinations, should be explored to evaluate an enhancement in immunogenicity and so in
the overall antibodies elicited. The second part of this thesis focuses on MeV, another major global health threat. As of August 2025, 32 measles outbreaks were officially reported in the United States (U.S.), with 92% of cases occurring in unvaccinated individuals. The rise of vaccine hesitancy contributes to a decrease in MeV vaccination, resulting in 10.3 million infected people worldwide in 2023. MeV is highly contagious and, since herd immunity has not been reached, poses a severe threat to all vulnerable populations who cannot receive the live-attenuated measles vaccine. Furthermore, when MeV infection happens in children less than 12 months old, the CNS experiences complications, including the lethal subacute sclerosing panencephalitis (SSPE), which occurs in the same children at a rate of 1:609, years after the disease has been cleared. In this thesis, an ‘antibody cocktail’ consisting of three anti-MeV humanized antibodies (77.1, Y10F, and H55) was initially tested in vitro to evaluate its potential for both prophylactic and therapeutic applications. Briefly, 77.1 binds to the pre-fusion conformation of the F MeV protein, stabilizing it in an intermediate state. Y10F recognizes the apex region of the F protein, locking the F in the pre-fusion conformation, while H55 binds the H protein, preventing the F protein from activating and interacting with the receptor. Therefore, combining all three antibodies resulted in a significant increase in inhibitory capacity, indicating a synergistic activity. Following, since MeV CNS complications are currently untreatable, a three amino acid modification (M252Y/S254T/T256E [YTE]) in the constant fraction (Fc) of 77.1 (77.1YTE) was tested in vivo to determine whether this modification would increase the antibody CNS localization in comparison to its unaltered version (77.1). As a result, 77.1YTE efficiently localizes in the CNS, remaining detectable still after 168 hours post-injection. Furthermore, 77.1YTE retains the ability to bind the natural conformation of the MeV F protein, suggesting that 77.1YTE could be efficient against CNS-adapted MeV viruses, representing a first significant advancement as a potential therapeutic approach
Genetic and environmental similarities drive repeated genomic evolution in Island Lizards
No full textRepeated adaptation provides valuable insights into the predictability of evolution. Population history, selection and stochastic processes can concur to generate a continuum from distinct to highly parallel evolutionary trajectories across replicate populations. Yet, the role of genetic and environmental factors in shaping this continuum remains underexplored. We quantified repeated genetic adaptation in lizards that colonised multiple islands with comparable environmental gradients, investigating whether environmental-dependent and divergence-dependent processes can explain the degree of repeated adaptation (genetic reuse and trajectory similarity). We found 149 genes exhibiting repeated adaptation in multiple islands, some of which are likely involved in thermal physiology and developmental processes. Genetic reuse was stronger at the functional level than at the mutation level and exceeded random expectations, highlighting that different genetic combinations can generate similar functional outcomes. Adaptive trajectories were more similar between islands with low genetic differentiation and similar environmental conditions, but the effects of genetic and environmental factors varied across the diverse facets of repeatability. Overall, our findings reveal the extent and conditions under which local adaptation is, in part, predictable
Un istituto negletto: il sequestro convenzionale
No full textL’articolo, dopo aver tratteggiato la nozione e le caratteristiche del contratto di sequestro convenzionale, si sofferma ad analizzare la sua funzione pratica, l’oggetto, i relativi presupposti, i diritti e le obbligazioni delle parti, facendo anche emergere le affinità e le differenze dell’istituto rispetto al trust di garanzia e all’escrow agreement
Optimizing robotic approach to ventral hernia repair: an updated systematic review and meta-analysis between preperitoneal versus retromuscular repair
No full textBackground: The Rives-Stoppa retromuscular repair remains the reference standard for open ventral hernia repair. Advances in robotic surgery have expanded the minimally invasive options for extraperitoneal mesh placement, enabling both retromuscular and preperitoneal approaches. The robotic ventral transabdominal preperitoneal repair (Rv-TAPP), has seen increasing adoption, but comparative evidence with the robotic retromuscular techniques remains limited. Methods: A systematic review and meta-analysis were reported in accordance with PRISMA and AMSTAR II guidelines (PROSPERO 2025: CRD420251173188). Searches of PubMed, Embase, Scopus, and Cochrane Library were searched to identify comparative studies evaluating robotic preperitoneal and retromuscular ventral hernia repair. Random-effects models (DerSimonian-Laird) were used to pool weighted mean differences (WMD) and risk ratios (RR) with 95% confidence intervals (CI). Results: Six retrospective studies including 3704 patients (2326 preperitoneal, 1378 retromuscular) were included. Preperitoneal cases involved smaller, predominantly primary defects (mean 3.0 cm vs 6.3 cm). Operative time was significantly shorter for Rv-TAPP (WMD = -39.4 min, 95% CI -58.5 to -20.2; p< 0.001). Overall postoperative complications occurred in 7.2% vs 15.6%, (RR= 1.65, 95% CI 1.21-2.26), with wound-related morbidity also lower with Rv-TAPP (RR = 1.81, 95% CI 1.25-2.63). Recurrence rates were comparable (1.9% vs 0.5%; RR = 0.95, 95% CI 0.29-3.11). Conclusions: Both robotic extraperitoneal approaches are safe and effective. Rv-TAPP offers shorter operative time and lower wound morbidity without increasing recurrence rates, favouring its use in small to medium-sized or primary ventral defects. Retromuscular repair remains preferred for large or complex hernias, underscoring their complementary roles in contemporary hernia repair
Targeting the histone-fold dimerization interface of oocyst rupture proteins from Plasmodium berghei for antimalarial inhibitor discovery
No full textDimerization between the histone-fold domains (HFD) of two Plasmodium Oocyst Rupture Proteins (ORP1 and ORP2) is essential for oocyst rupture in the Anopheles mosquito vector host, representing a key event in parasite transmission to humans. Notably, ORPs are a rare example of HFD-containing proteins that operate outside the nucleus and that lack DNA-binding functions, typically associated with core histones and transcription factors hosting deviant histones. ORP HFD heterodimerization occurs at the outer capsule of the oocyst, immediately prior to rupture, thus providing a temporal window to administer dimerization blocking molecules. In this context, we present the first detailed structural analysis of the HFD ORP heterodimer, solved by X-ray crystallography at 3.1 Å resolution, and analyze the oligomerization interface as a possible druggable target. Targeting the mosquito phase of the parasite lifecycle remains an under-exploited avenue as present antimalarial therapies mainly target the human blood stages of infection. We employed a GAL4-based yeast two-hybrid (Y2H) combinatorial library of cyclic peptides (CPs) to identify six candidates that inhibit dimerization in vitro. Molecular docking simulations confirmed that all six CPs bind at the dimer interface, allowing us to rank them for further in vivo testing of their efficacy in blocking oocyst rupture
The role of plaque morphology and composition in vulnerability assessment: Computational analysis using CT images and elastography
No full textObjective This study seeks to assess the influence of using patient-specific data from different imaging methods on evaluating carotid plaque vulnerability via finite element analysis (FEA) instead of using data derived from the literature. Methods 54 patients were considered in this analysis, who preoperatively underwent computed tomography angiography (CTA) and ultrasound (US) imaging evaluations. The composition (i.e. calcific, lipidic and mixed) and vulnerability (i.e. stable or vulnerable) of their plaques were evaluated by macroscopic and histologic assessment post-endarterectomy. In particular, the plaques of these 54 patients were classified as mixed. 3D reconstructions of the carotid artery were generated from CTA scans, and computational analyses were performed using two different simulation settings for material properties and loads: a) the material properties of the plaque components were set as an average of values available in the literature (LIT-based); b) the material property of the plaque fibrous content was modified using stiffness data derived from US shear-wave elastography imaging (SWE-based). Statistical analyses were conducted to compare stress parameters obtained from the different simulations within groups of vulnerable and stable plaques. Results Comparisons between LIT-based and SWE-based FEA revealed notable differences in stress parameters associated with plaque vulnerability. In particular, the stress values derived from SWE-based simulations provided distinct stratification of vulnerable versus stable plaques, whereas LIT-based models showed limited differentiation. Significant variations in von Mises ( p = 0.015, p = 0.037) and maximum principal stress ( p = 0.014) distributions were observed in SWE-based FEA. Conclusions Patient-specific modelling and computational analysis integrating CTA-derived morphological with US-derived biomechanical data could improve the assessment of plaque vulnerability in mixed-composition carotid plaques
Meat superchilling monitoring by NIR: penetration limits and multivariate charts
No full textNear-infrared spectroscopy offers promising non-destructive monitoring for food processing, but its effectiveness depends on both signal penetration and real-time detection of physiochemical changes. Therefore, this study investigates three key aspects of NIR application in meat superchilling: (i) assessing the thermal stability of the MicroNIR device under process conditions, (ii) evaluating the penetration depth of NIR signal in pork, beef and chicken tissues, and (iii) developing multivariate statistical control charts (MSCC) to monitor freezing dynamics through water-related spectral changes. Penetration depth was assessed by placing meat slices (2.5–30 mm) between polypropylene and a MicroNIR sensor, determining the maximum detectable depth. In a parallel experiment, cubed meat samples (30 × 30 × 30 mm) underwent controlled superchilling with spectra collected every 2 min and analysed through principal component analysis (PCA) and aquaphotomics. The MicroNIR demonstrated signal stability under varying temperature conditions, confirming its suitability for in-line monitoring. Results showed NIR penetrates up to 5 mm under refrigeration conditions, with reduced effectiveness under freezing. However, this was enough to detect the thin frozen surface layer characteristic of superchilling. Spectral variations during the process showed consistent trends, particularly in the water-related band. PCA highlighted key water phase transitions, while aquagrams mapped water structuring. MSCCs based on PCA and aquaphotomic markers reliably identified superchilling start and end in real time, closely matching temperature-based references. This work not only clarifies the effective penetration limits of NIR in refrigerated and frozen muscle tissues, but also proposes a robust, automatable strategy for process monitoring based on the spectral behaviour of water